Elucidation of the mechanisms that specify cardiac muscle cell fate is one of the central issues in cardiovascular biology. We have recently discovered a novel transcription factor, named myocardin, which is expressed specifically in embryonic and adult cardiac and smooth muscle cells. Myocardin belongs to the SAP domain family of nuclear proteins and activates cardiac and smooth muscle genes by associating with serum response factor (SRF), a widely expressed MADS box transcription factor that regulates differentiation and proliferation of muscle cells. Expression of a dominant negative mutant of myocardin in Xenopus embryos interferes with heart formation and myocardial cell differentiation, and ectopic expression of myocardin induces cardiac and smooth muscle gene expression. The overall goal of this project is to define the mechanisms whereby myocardin regulates cardiac and smooth muscle development and to identify regulatory factors and signaling systems that govern myocardin activity and expression. These studies will provide fundamental insights into the mechanisms involved in cardiovascular development and disease, and should advance strategies for regeneration and repair of the cardiovascular system.